A variety of human diseases demonstrate amyloid deposition and often involve systemic organs (i.e. organs or tissues lying outside the central nervous system), with the amyloid accumulation leading to organ dysfunction or failure. In these amyloid diseases, a single organ may be affected such as the pancreas in 90% of patients with type 2 diabetes. In this type of amyloid disease, the beta-cells in the islets of Langerhans in pancreas are believed to be destroyed by the accumulation of fibrillar amyloid deposits consisting primarily of a protein known as islet amyloid polypeptide (IAPP) or amylin. Specifically the islet is depleted in beta-cell mass due to beta-cell apoptosis and islet amyloid. In vitro studies have shown that amyloidogenic human IAPP is toxic to cultured beta-cells (Lorenzo, A., et al., Nature 368:756-760, 1994). In monkey's islet amyloid deposition has been temporally correlated with the onset of hyperglycemia (Howard, C. F. Diabetologia 29:301-306, 1986). A transgenic mouse model is available with increased human IAPP transgene expression which leads to beta-cell apoptosis and diabetes in the model animal (Matveyenkp A V and Butler P C. ILAR J. 47(3):225-233, 2006). Inhibiting or reducing such IAPP amyloid fibril formation, deposition, accumulation and persistence may be beneficial for the treatments for type 2 diabetes.
Discovery and identification of new compounds or agents as potential therapeutics to arrest amyloid formation, deposition, accumulation and/or persistence that occurs in IAPP amyloid disease, such as type 2 diabetes, are sought.